Results Fourteen articles reported populations subjected to cooling treatment for classic or exertional heatstroke and included data on cooling time, neurologic morbidity, or mortality..
Trang 1Open Access
Vol 11 No 3
Research
Cooling and hemodynamic management in heatstroke: practical recommendations
Abderrezak Bouchama1, Mohammed Dehbi1 and Enrique Chaves-Carballo2,3
1 Department of Comparative Medicine MBC-03, King Faisal Specialist Hospital & Research Centre, P.O Box 3354, Riyadh 11211, Saudi Arabia
2 Department of Neurosciences MBC-76, King Faisal Specialist Hospital & Research Centre, P.O Box 3354, Riyadh 11211, Saudi Arabia
3 Departments of Pediatrics and History and Philosophy of Medicine, Kansas University Medical Center, Kansas, USA
Corresponding author: Abderrezak Bouchama, abouchama@kfshrc.edu.sa
Received: 3 Feb 2007 Revisions requested: 23 Mar 2007 Revisions received: 12 Apr 2007 Accepted: 12 May 2007 Published: 12 May 2007
Critical Care 2007, 11:R54 (doi:10.1186/cc5910)
This article is online at: http://ccforum.com/content/11/3/R54
© 2007 Bouchama et al.; licensee BioMed Central Ltd
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction Although rapid cooling and management of
circulatory failure are crucial to the prevention of irreversible
tissue damage and death in heatstroke, the evidence supporting
the optimal cooling method and hemodynamic management has
yet to be established
Methods A systematic review of all clinical studies published in
Medline (1966 to 2006), CINAHL (Cumulative Index to Nursing
& Allied Health Literature) (1982 to 2006), and Cochrane
Database was performed using the OVID interface without
language restriction Search terms included heatstroke,
sunstroke, and heat stress disorders
Results Fourteen articles reported populations subjected to
cooling treatment for classic or exertional heatstroke and
included data on cooling time, neurologic morbidity, or mortality
Five additional articles described invasive monitoring with
central venous or pulmonary artery catheters The four clinical
trials and 15 observational studies covered a total of 556
patients A careful analysis of the results obtained indicated that the cooling method based on conduction, namely immersion in iced water, was effective among young people, military personnel, and athletes with exertional heatstroke There was no evidence to support the superiority of any one cooling technique
in classic heatstroke The effects of non-invasive, evaporative, or conductive-based cooling techniques, singly or combined, appeared to be comparable No evidence of a specific endpoint temperature for safe cessation of cooling was found The circulatory alterations in heatstroke were due mostly to a form of distributive shock associated with relative or absolute hypovolemia Myocardial failure was found to be rare
Conclusion A systematic review of the literature failed to identify
reliable clinical data on the optimum treatment of heatstroke Nonetheless, the findings of this study could serve as a framework for preliminary recommendations in cooling and hemodynamic management of heatstroke until more evidence-based data are generated
Introduction
Heatstroke is a life-threatening condition characterized by a
rapid increase in core temperature to more than 40°C and
widespread, multiple organ tissue injury It is a leading cause
of mortality and neurologic morbidity when there is an
unac-customed and sustained increase in climatic temperature
[1-4] During the heat wave that affected Europe in August 2003,
there were 14,800 victims in France alone, and 4,277 (28.9%)
of these victims were diagnosed as having heatstroke,
hyper-thermia, or dehydration [4] As sophisticated climate models
predict an increased frequency and severity of heat waves, the
incidence of heatstroke with an outcome of mortality or
neuro-logic morbidity is expected to rise if proactive measures are not taken [5,6] Heatstroke occurs in epidemic form during heat waves, and both hospital emergency department visits and intensive care unit (ICU) admissions increase sharply Health care professionals should be adequately prepared to promptly recognize and treat this life-threatening illness Laboratory studies using cell lines and animal models have established that heat directly induces tissue injury and that the severity of tissue injury and cell death is a function of the degree and duration of hyperthermia [7-10] Clinical studies have shown that death from heatstroke mostly occurs soon after the onset of hyperthermia and associated cardiovascular failure [11-14] Up to one third of those victims who survive
BCU = body cooling unit; CVP = central venous pressure; ICU = intensive care unit.
Trang 2these initial deleterious effects progress to multi-organ system
failure culminating in death or severe neurologic damage
[15,16] The most important objectives in the treatment of
heatstroke are, therefore, to decrease body temperature as
quickly as possible and to support the cardiovascular system
Achievement of these goals is crucial to the prevention of
irre-versible organ damage and death
Effective dissipation of heat is accomplished by increasing the
temperature gradient (conduction), water vapor pressure
(evaporation), and velocity of air (convection) between the skin
and the surrounding air [1,17] Several techniques have been
devised based on these principles, including immersion in cold
water, placement of cold packs or ice slush over parts of or the
whole body, the use of cooling blankets, and wetting the body
surface while continually fanning [16-30] These cooling
tech-niques have been used for decades, but the evidence
support-ing their safety and effectiveness in rapidly reachsupport-ing a safe
body temperature and reducing morbidity and mortality has yet
to be evaluated
Acute circulatory failure is found in 20% to 65% of patients
with heatstroke and has been implicated in the aggravation of
tissue injury and cell death [12,13,16,31,32] The cause of
this failure is not well understood but has been attributed
var-iously to pooling of blood into the cutaneous circulation [31],
volume loss by evaporation and insufficient intake of fluid
[14,31], myocardial damage [13,33], and distributive shock
resembling that of sepsis [34] Accordingly, several treatment
modalities have been proposed without adequate supporting
evidence [1,14,34-36] The objective of this report is to
present a systematic review of the literature which addresses
these central phases of care, for the purpose of developing
evidence-based practice guidelines for cooling and
hemody-namic support in heatstroke, especially classic heatstroke
Materials and methods
Search strategy
We searched the National Library of Medicine's Entrez
PubMed databases for the period 1966 to April 2006, the
CINAHL (Cumulative Index to Nursing & Allied Health
Litera-ture) for the period 1982 to April 2006, the Cochrane
Data-base of Systematic Reviews, and the Cochrane Central
Register of Controlled Trials Register using the OVID
inter-face We also manually searched reference lists The retrieved
references were downloaded into a reference manager
The search was limited to human studies without language
restriction and used the MeSH (Medical Subject Heading)
terms heatstroke, sunstroke, and heat stress disorders
Selection criteria
Two of the authors independently evaluated the retrieved
arti-cles and made selections based on the population,
interven-tion, outcome, and study design
Cooling methods
We examined adult and pediatric populations who had classic
or exertional heatstroke and who were subjected to cooling treatment in studies that reported cooling time and neurologic morbidity or mortality as endpoints To be eligible for review, the study had to report original data and consist of randomized controlled studies or observational studies (cohort or descrip-tive studies, case-control, and case series) involving more than
10 patients
Exclusion criteria included (a) studies reporting only biochem-ical and/or immunologbiochem-ical endpoints (that is, clinbiochem-ical chemistry, hormones, cytokine levels, and immune cell responses), (b) heat stress disorders (that is, occupational or induced whole-body hyperthermia), (c) reviews, case reports, and case series
of fewer than 10 patients, and (d) experimental studies using healthy volunteers or animal models
Hemodynamic management
Adult and pediatric populations with classic or exertional heat-stroke who were monitored invasively with central venous or pulmonary artery catheters and reporting right- or left-filling pressures or cardiac output as endpoints were examined To
be eligible, the studies must have reported original data in more than five patients
Endpoints and definitions
Heatstroke is defined as a core body temperature rising to more than 40°C and central nervous system abnormalities such as delirium, convulsions, and/or coma resulting from exposure to a high environmental temperature (classic or non-exertional heatstroke) or strenuous physical exercise (exer-tional heatstroke) Table 1 presents common and distinctive features of classic and exertional heatstroke [1] Cooling is defined as physical methods or pharmacologic agents aimed
at accelerating cooling to a predefined target temperature Neurologic morbidity is defined as sustained central nervous system abnormalities such as delirium, convulsions, and coma following cooling and/or during long-term follow-up in survivors
Results Search results
The search identified 926 papers on heat illnesses From these, four randomized controlled studies [26,28-30] and 10 observational studies met the eligibility criteria for the evalua-tion of cooling methods [16,18-,27] Seven studies that used cooling method based on conduction were identified, five on evaporation and two on pharmacologic cooling Various target temperatures ranging from 37°C to 40.1°C for safe discontin-uation of cooling were used Five observational studies met the criteria for the assessment of hemodynamic management [31,34,37-39] The total number of patients reported in these
19 publications was 556, and these were subjected to further analysis (Tables 2, 3, 4, 5, 6)
Trang 3Cooling methods based on conduction
Conduction is the passive transfer of heat from the body into
the surroundings air, liquid, or solid in contact with the skin
along a temperature gradient
1 Exertional heatstroke
Immersion in iced water
This is the most used conventional cooling technique and
involves placing the patient in a tub of iced water and
continu-ously massaging the extremities to promote vasodilatation and
heat loss [11,12,16,19,21] Four studies that used this
method in patients with exertional heatstroke were identified
[19-21,30] Table 2 presents a summary of data on cooling
methods based on conduction in the treatment of exertional
heatstroke
Three of the studies included 41 young military personnel
treated with immersion in iced water to a target temperature of
between 38.3°C and 38.8°C [19-21] (Table 2) The cooling
time ranged from 10 to 60 minutes in all patients but one No
fatalities were reported Neurologic morbidity, characterized
by marked confusion, violent behavior, and frank psychosis,
was present during recovery but subsided subsequently [20]
The fourth study was a prospective comparison of immersion
of the torso and thighs in iced water (1°C to 3°C), with
evaporative cooling using wet towels and exposure to air at
24.4°C without fan ventilation, in hyperthermic long-distance
runners [30] The immersion technique cooled twice as fast as
the evaporative technique Morbidity, mortality, and follow-up
were not reported The assignment of patients to each arm of
treatment was not randomized, and the evaporative cooling
technique was not optimal (Table 2)
Application of cold packs
One study in which 36 patients were treated with cold packs applied to the whole body was identified No cooling time was provided, but mortality and neurologic morbidity in survivors were 22.2% and 11.1%, respectively [18] (Table 2)
2 Classic heatstroke
Table 3 presents a summary of data on cooling methods based on conduction in the treatment of classic heatstroke
Immersion in iced water
This was applied to 28 patients of a mean age of 71 years (range, 47 to 90 years) with associated comorbid illnesses [16] The cooling rate achieved was comparable with that of the younger and healthier population described above; however, 14.3% of the patients died and another 14.3% sus-tained severe brain damage The technique was poorly toler-ated and had to be converted to ice massage in some patients, who were not further identified
Other cooling methods based on conduction
These included non-invasive and invasive techniques The former comprised the use of cooling blankets or ice or cold packs covering all or parts of the body, commonly in proximity
to large vessels (that is, neck, groin, and axillae) [1] The inva-sive techniques consisted of administration of chilled intrave-nous solution and iced gastric, colonic, bladder, or peritoneal lavage
A single study that consisted of 39 patients treated with cold packs was identified [24] (Table 2) Thirty-one of the 39 patients had cold packs applied to the axillae and groin and cold wet sheets applied to the trunk; this was combined with
Table 1
Common and distinctive features of classic and exertional heatstroke
Common
Distinctive
Trang 4cooling blankets in four patients and with ice water lavage in
five patients The overall mortality rate was 20.5% A cooling
time of less than 60 minutes was achieved in 27 patients
(69%) with a mortality rate of 15%, whereas in the group with
a longer cooling time, the mortality rate was 33% Although the
difference was not statistically significant, this observation
suggests that rapid cooling may be an important determinant
of outcome There were insufficient data to assess the value of
invasive cooling techniques
Cooling methods based on evaporation
Evaporative cooling is based on the physical principle that the conversion of 1.7 ml of water to a gaseous phase consumes 1 kcal of heat [1,11] The efficiency of evaporative cooling depends on a high water-vapor pressure gradient accom-plished by continuously spraying the skin with water and blow-ing with hot air to keep it warm [1,17]
Summary of data on cooling methods based on conduction in the treatment of exertional heatstroke
Study
(country, year)
Population Study design Intervention Outcomes measured Results Limitations
[18] (Israel, 1967) Exertional heatstroke
(n = 36) Case series Ice-filled rubber bottles over the
whole body; cool air-conditioned room;
target Trect: not given
Mortality; morbidity Mortality: 22.2%;
neurologic morbidity:
11.1%
Patients enrolled over 10-year period;
no cooling time provided; cooling performed in different centers [19] (U.S., 1975) Exertional heatstroke
(n = 15)
Case series Iced water
immersion; target
Trect: 38.8°C
Mortality; morbidity Mortality: 0%;
neurologic morbidity:
0%
None
[20] (U.S., 1975) Exertional heatstroke
(n = 13) Case series Iced water immersion; target
Trect: 38.3°C
Cooling time;
mortality; morbidity Cooling time: < 60 minutes, 92.3%;
cooling time: > 60 minutes, 7.7%;
mortality: 0%;
neurologic morbidity:
0%
None
[21] (U.S., 1979) Exertional heatstroke
(n = 13) Case series Iced water immersion; target
Trect: 38.3°C to 38.8°C
Cooling time;
mortality; morbidity Cooling time (range): 10 to 40 minutes;
myocardial ischemia:
7.7%; neurologic morbidity: 0%;
mortality: 0%
None
[30] (U.S., 1996) Exertional heatstroke
(n = 21) Randomized controlled trial Iced water immersion (1°C to 3°C) torso
and upper legs (n =
14) versus wet towel and air exposure at
24.4°C (n = 7);
target Trect: 38.2°C
to 40.1°C
Cooling rate Conductive-based
cooling faster than evaporative (0.20 ± 0.02 versus 0.11 ± 0.02°C/minute)
Small sample size; comparability of baseline characteristics undetermined; randomization method not specified;
evaporative technique suboptimal
Trect: rectal temperature.
Table 3
Summary of data on cooling methods based on conduction in the treatment of classic heatstroke
Study
(country, year)
Population Study design Intervention Outcomes measured Results Limitations
[16] (U.S., 1982) Classic heatstroke
(n = 28) Case series Iced water immersion; brisk
massage with ice;
target Trect: ≤38.9°C
Cooling time;
mortality; morbidity Cooling time: < 30 minutes, 93%; cooling
time: 30 to 45 minutes, 7%; mortality: 14.3%;
neurologic morbidity:
14.3%
Patients switched to brisk massage were not identified
[24] (U.S., 1986) Classic heatstroke
(n = 39) Case series Ice packs to axilla and groin; cold wet
sheets applied to torso; ice water lavage; cooling blankets; target T rect :
≤38.9°C
Cooling time;
mortality Cooling time: < 60 minutes, 69%; mortality:
15%; cooling time: > 60 minutes, 31%; mortality:
33%;
Retrospective assignment
of group; comparability of the groups at baseline questionable
Trect: rectal temperature.
Trang 5Exertional heatstroke
Other than the study mentioned above [30], no study
describ-ing the use of the evaporative cooldescrib-ing technique in exertional
heatstroke was found (Table 2)
Classic heatstroke
Five studies comprising 247 patients treated by evaporative
cooling techniques, either conventional or by using a specially
designed cooling bed, were identified [22,23,25-27] Table 4
presents a summary of data on cooling methods based on
evaporation in the treatment of classic heatstroke
Conventional evaporative cooling
This consists of applying gauze sheets wetted with water at
20°C to 40°C and fanning air at room temperature In a case
series of 14 patients of a mean age of 66 years and who had
associated comorbid illnesses, cooling by evaporation using
water at 40°C and fan ventilation enabled cooling in 34 to 89
minutes, with only one fatality and no morbidity in survivors
[25] In this study, the evaporative method was combined with
conductive techniques, namely cooling blanket, gastric,
colonic and bladder lavage with iced saline, and intravenous
administration of chilled solutions; thus the relative
contribu-tion of each modality was difficult to assess
In another series (n = 25 patients) using a similar method but
applying wet gauze at 20°C, the cooling time ranged from 20
to 145 minutes, with no mortality Six (25%) patients pro-gressed to dysfunction of one or more organs with no further follow-up [27]
Evaporative cooling using body cooling unit
The body cooling unit (BCU) is a bed specially constructed to combine spraying of atomized water at 15°C and blowing of hot air at 45°C over the whole body surface to keep the wet skin temperature between 32°C and 33°C [40] The BCU has been used extensively during the Muslim pilgrimage to Makkah, Saudi Arabia, in the summer months, when the inci-dence of heatstroke rises markedly [23] A total of three stud-ies using the BCU were identified [22,23,26] (Table 4) The first two studies comprised 192 patients suffering from classic heatstroke [22,23] The cooling time to reach a target temperature of 38°C ranged from 26 to 300 minutes (mean,
78 minutes) The mortality rate varied between 11.1% and 14.9% No neurologic morbidity post-cooling was observed among survivors
The third was a controlled study that compared conventional evaporative cooling with cooling using the BCU [26] The
Table 4
Summary of data on cooling methods based on evaporation in the treatment of classic heatstroke
Study
(country, year)
Population Study design Intervention Outcomes measured Results Limitations
[25] (U.S., 1986) Classic heatstroke
(n = 14) Case series Ice to the lateral aspect of the trunk
and spraying of tepid water (40°C); fan directed to patients;
massage to torso and neck; chilled intravenous solution;
target Trect: ≤ 39.4°C
Cooling time;
mortality; morbidity Median (range) cooling time: 60
minutes (34 to 89 minutes); mortality:
7.1%; neurologic morbidity: 0%
Combination of several cooling techniques; relative contribution of each difficult to ascertain
[27] (Saudi Arabia,
1987) Classic heatstroke(n = 25) Case series Wet gauze sheet with water at 20°C;
fan with speed airflow of 2.6 m/s;
target Trect: ≤ 39°C
Cooling time;
mortality; morbidity Mean (range) cooling time: 40.4 minutes
(20 to 145 minutes);
mortality: 0%;
morbidity: 24%
No follow-up
[22] (Kuwait, 1980) Classic heatstroke
(n = 18)
Case series Body cooling unit*;
target Trect: < 38°C
Cooling time;
mortality;
Cooling time: 26 to
300 minutes;
mortality: 11.1%
No follow-up
[23] (Kuwait, 1981) Classic heatstroke
(n = 174)
Case series Body cooling unit*;
target Trect: < 38°C
Cooling time;
mortality;
Mean (range) cooling time: 78 minutes (20
to 180 minutes);
mortality: 14.9%
No follow-up
[26] (Saudi Arabia,
1986) Classic heatstroke(n = 16) Randomized controlled trial Evaporative cooling using body cooling
unit* (n = 8) versus
conventional method (wet gauze sheet with water at 25°C and fanning air at
20°C) (n = 8); body
cooling unit*; target
Trect: ≤ 38.5°C
Cooling time;
mortality; morbidity No significant difference in cooling
time; no death in either group;
neurologic morbidity:
25% versus 12.5%
Small sample size; randomization method not specified; no follow-up
Trect: rectal temperature.
*A special bed preset to spray atomized water at 15°C and warm air at 45°C over the whole body surface to keep the wet skin temperature between 32°C and 33°C [40].
Trang 6small sample size precluded any meaningful interpretation of
the data
Cooling methods based on medications
Dantrolene sodium is a skeletal muscle relaxant that reduces
muscular heat produced during abnormally sustained
contrac-tion such as observed in malignant hyperthermia and
neu-roleptic malignant syndrome [28,29,41] It acts directly on the
skeletal muscle and is thought to inhibit calcium release from
the sarcoplasmic reticulum to the cytosol during sustained
contraction and thereby reverses muscle rigidity and
decreases production of heat [41,42] Table 5 presents a
summary of data on pharmacologic cooling in the treatment of
classic heatstroke Two randomized controlled studies
assessed the cooling enhanced pharmacologically by using
dantrolene sodium [28,29]
In a randomized study of 20 patients, 2 to 4 mg/kg dantrolene
sodium plus evaporative cooling was found to reduce
signifi-cantly the cooling time compared with evaporative cooling
alone [28] However, flaws in the study design (namely, a small
number of patients and an undefined randomization procedure
with the use of different cooling techniques and doses of
dantrolene sodium, which were non-blinded to clinicians) raise
doubts about the scientific validity of the results
In contrast, the second study of 52 patients was
double-blinded, randomized, and adequately powered to demonstrate
a 30-minute difference in cooling time This study showed that
2 mg/kg dantrolene sodium was ineffective in reducing the
cooling time, length of hospital stay, and mortality (Table 5)
[29]
Antipyretic drugs were used following the findings of
increased pyrogenic cytokines during heat stress [1] These
were given to few patients with heatstroke and concomitantly
with other cooling techniques, and thus their effectiveness
could not be properly assessed [15]
Hemodynamic support
The hemodynamic response to heat stress has been well stud-ied both in supine, resting, healthy volunteers heated to the limits of thermal tolerance and during exercise in a hot environ-ment [43] The circulatory adjustenviron-ments were comparable but differed in magnitude and muscular perfusion, which were more marked for the latter These changes included a marked increase in cardiac output accompanied by redistribution of blood flow to the cutaneous circulation (up to 50% of cardiac output) at the expense of renal and splanchnic circulation, while total peripheral vascular resistance remained unchanged [43] Studies in animal experiments suggest that secondary splanchnic vasodilation mediated by local production of nitric oxide results in cardiovascular collapse and hyperthermia [44,45] In contrast, the hemodynamic alterations that follow heatstroke have not been completely elucidated [31,34,37-39]
The search strategy used for this review yielded five studies on the hemodynamic alterations in heatstroke with monitored response to therapy [31,34,37-39] Table 6 presents a sum-mary of data on hemodynamic monitoring and support in heatstroke
Hemodynamic alterations in exertional heatstroke
O'Donnell and Clowes [34] performed serial hemodynamic measurements in eight marine soldiers suffering from acute exertional heatstroke Seven of the patients displayed an ele-vated cardiac index and low systemic vascular resistance In one patient, cardiac index was low and systemic and pulmo-nary vascular resistances were elevated with a marked increase in right atrial pressure (Table 6)
Hemodynamic alterations in classic heatstroke
By means of right heart catheterization, the hemodynamic pro-file of 30 elderly patients suffering from classic heatstroke was investigated in three studies [31,37,38] (Table 5) Twenty-three (76.6%) of the patients exhibited a hyperdynamic profile,
Summary of data on pharmacologic cooling in the treatment of classic heatstroke
Study
(country, year)
Population Study design Intervention Outcomes measured Results Limitations
[28] (Saudi Arabia,
1990) Classic heatstroke(n = 20) Randomized controlled study Evaporative cooling + dantrolene 2 to 4
mg/kg IV (n = 8)
versus evaporative
cooling alone (n =
12); target Trect: ≤ 38.9°C
Cooling time;
mortality; morbidity Cooling time in the dantrolene group
lower than control (49.7 ± 4.4 versus 69.2 ± 4.8 minutes;
p < 0.01); no
difference in morbidity and mortality
Small sample size; randomization method not specified;
comparability of baseline characteristics questionable
[29] (Saudi Arabia,
1991) Classic heatstroke (n = 52) Randomized controlled study Evaporative cooling + dantrolene 2 mg/
kg IV (n = 26) versus
evaporative cooling
+ placebo (n = 26);
target Trect: ≤ 39.4°C
Cooling time; organ dysfunction; length
of hospital stay;
mortality
No significant difference between study and control groups for any of the endpoints
None
IV, intravenous; T rect : rectal temperature.
Trang 7and 6 (20%) a hypodynamic profile The clinical response to
fluid therapy and the risk of pulmonary edema varied among
studies, thus precluding any meaningful interpretation
In the last study, the state of hydration and response to a
con-servative fluid challenge were prospectively assessed with
central venous pressure (CVP) monitoring in 34 consecutive
patients with classic heatstroke [39] Twelve patients had a
CVP reading of zero or less on arrival, and eight of these
patients presented in shock state Administration of an
aver-age of 1 liter (0.5 to 2.5 liters) of crystalloids titrated to a CVP
not result in any signs of fluid overload
Discussion
Cooling methods
The present study evaluated various cooling techniques used
to treat heatstroke We made the following observations:
First, consistent with a previous systematic review, the cooling
method based on conduction, namely immersion in iced water
started within minutes of the onset of exertional heatstroke,
was fast, safe, and effective in young, healthy, and well-trained
military personnel or athletes [19-21,30,46] Furthermore,
when extending the analysis to classic heatstroke, this study
demonstrated that immersion in iced water of elderly patients
suffering from classic heatstroke had a comparable efficacy in
achieving a high cooling rate, but the technique was poorly tol-erated and was associated with increased morbidity and mor-tality [16] These findings concurred with those of earlier studies in which severe shivering, agitation, and combative-ness required the mobilization of a large number of staff for restraint and in which sedation was necessary [11,12,20] Other drawbacks reported were poor hygiene (heatstroke is often associated with vomiting and diarrhea) and difficulty both
in achieving optimal monitoring and resuscitating unconscious and hemodynamically unstable patients [11,20]
Second, although none of the randomized controlled studies compared evaporative with conductive cooling methods in patients with classic heatstroke, the cooling methods based
on evaporation appeared to be less efficient than immersion in iced water in dissipating heat, but they were well tolerated [22,23,25,26,28,29] Despite a slower cooling rate, the mor-tality rate was low, ranging from 0% to 14.9% [22,23,25,26,28,29] For many reasons – such as heteroge-neity of the population studied, lack of information on the time required to recognize heatstroke and initiate cooling, and com-parability of supportive management – how this favorable out-come compared with that of cooling by immersion in iced water is difficult to ascertain Until randomized controlled stud-ies comparing these two modalitstud-ies of cooling treatment are performed, each should be considered an equivalent option in the treatment of classic heatstroke Perhaps the final choice
Table 6
Summary of data on hemodynamic monitoring and support in heatstroke
Study
(country, year)
Population Intervention Outcomes measured Results
[34] (U.S., 1972) Exertional heatstroke
(n = 8) Pulmonary artery catheter; fluid therapy Hemodynamic profile; response to fluid therapy;
mortality
Hyperdynamic profile, n = 7; hypodynamic profile, n = 1;
optimal response to fluid: 1,200 ml per 4 hours and cooling; mortality: 0% [31] (U.S., 1979) Classic heatstroke
(n = 7) Pulmonary artery catheter; fluid therapy Hemodynamic profile; response to fluid therapy;
mortality
Hyperdynamic profile, n = 2; hypodynamic profile, n = 5;
failure to respond to fluid: 6,000 ml per 24 hours and cooling; no pulmonary edema; mortality: 71%
[37] (Saudi Arabia, 1989) Classic heatstroke
(n = 13)
Pulmonary artery catheter; fluid therapy
Hemodynamic profile;
response to fluid therapy;
mortality
Hyperdynamic profile, n = 13;
fluid 400 to 1,200 ml per 4
hours, n = 8, no pulmonary
edema; fluid 1,200 to 1,800 ml
per 4 hours, n = 5, pulmonary
edema; mortality: 7.6% [38] (Saudi Arabia, 1993) Classic heatstroke
(n = 10)
Pulmonary artery catheter Hemodynamic profile; mortality Hyperdynamic profile, n = 8;
hypodynamic profile with normal systemic vascular
resistance, n = 1;
normodynamic profile, n = 1;
mortality: 10%
[39] (Saudi Arabia, 1991) Classic heatstroke
(n = 34)
CVP monitoring; fluid therapy CVP; response to fluid
therapy; mortality
CVP < 3 cm H2O, n = 12
(35.3%); CVP 3 to 10 cm
H2O, n = 16 (47%); CVP >10
cm H2O, n = 6 (17.6%); fluid
500 to 2,500 ml titrated to CVP (3 to 8 cm H2O); optimal response, no pulmonary edema; mortality: 0% CVP, central venous pressure.
Trang 8should depend on the patient's condition, the availability of
equipment, and the staff's familiarity with the selected
technique
Third, our review showed that non-invasive and well-tolerated
cooling modalities, such as ice packs or cold packs, wet gauze
sheets, and fan alone or in combination, could represent
rea-sonable alternatives since these are easily applied and readily
accessible during epidemic classic heatstroke, when a large
number of frail elderly patients are seen in the emergency room
[24-27] Indeed, in four studies, the cooling time using these
techniques in patients with classic heatstroke was reasonably
low and the outcome was acceptable [24-27]
Fourth, this review suggested that pharmacologic treatment
(namely, dantrolene sodium as an adjunct to physical methods
to accelerate cooling) was ineffective, whereas antipyretic
agents were not properly assessed [28,29] Antipyretics such
as aspirin and acetaminophen should be avoided because of
their potential to aggravate the coagulopathy and liver injury of
heatstroke
Fifth, our review found no evidence for a specific endpoint
temperature at which to halt cooling A rectal temperature of
39°C or less appeared to be safe in terms of mortality in most
of the studies, but associated long-term morbidity (particularly
neurologic) has not yet been established and further study is
required
Hemodynamic management
Although rapid and effective cooling is the cornerstone of
treatment, the management of circulatory failure in heatstroke
is also important [12-14,16] In an earlier study of 100 patients
with classic heatstroke, Austin and Berry [12] showed that
hypotension was associated with a mortality rate of 33%
com-pared with 10% in patients without hypotension Hart and
col-leagues [16] found that the necessity for supplementary
vasoactive treatment to restore blood pressure was
associ-ated with both a high mortality rate and neurologic disability
These observations were reinforced by a recent survey of 345
patients with classic heatstroke which demonstrated that the
use of vasoactive drugs within the first 24 hours of admission
to the ICU was independently associated with an increased
risk of death [32] These findings established a link between
hypotension and poor outcome, suggesting that prevention
and treatment of the hemodynamic instability of heatstroke
may contribute to improved outcome
Based on available data, the present study established the
fol-lowing evidence:
The circulatory alterations and collapse in both exertional and
non-exertional heatstroke were, for the most part, due to a form
of distributive shock characterized by vasodilatation and
rela-tive or absolute hypovolemia [31,34,37,38] A hypodynamic
state was observed in approximately 20% of the patients [31,38] Although myocardial failure appeared only rarely, the presence of myocardial dysfunction at the onset of heatstroke seemed more difficult to ascertain in an elderly population with
a high prevalence of pre-existing coronary or structural cardiac diseases [33,34,47,48] Overall, the findings of our study sug-gested that the hemodynamic profile of heatstroke shares many similarities with sepsis and is consistent with the sys-temic inflammatory response demonstrated in human and experimental heatstroke [1,49]
In contrast to the findings on the hemodynamic profile, the data on the risk of pulmonary edema were inconclusive The varying amount of fluid administered in different studies did not explain why some patients developed pulmonary edema and others did not There were numerous confounding factors such comorbid illness, acute lung injury, and/or heat-related myocardial damage that may be associated with heatstroke and could have accounted for this difference
Although the present systematic review showed that hypoten-sion could impact negatively on outcome, there was even less evidence to support the concept that restoration of blood pressure would ameliorate the outcome The findings of this review suggested that besides cooling, the initial hemody-namic management in both exertional and classic heatstroke should include fluid replacement sufficient to restore blood pressure and tissue perfusion Supporting evidence, however,
is lacking for more specific recommendations, such as the selection of a specific type of fluid and the rate and volume of infusion, and so careful fluid replacement is recommended as the incidence of pulmonary edema during resuscitation of heatstroke appeared to be high in some studies [37-39] Until new evidence is established, the therapeutic approach recom-mended for hemodynamic management of sepsis can also be applied to heatstroke because of the pathophysiological simi-larities between the two diseases [50] Fluid resuscitation should be titrated to clinical endpoints of optimal heart rate, urine output, and blood pressure, and the patients who remain hypotensive after initial fluid and cooling therapy should be considered for invasive hemodynamic monitoring
Limitations
This review identified the lack of reliable data from well-designed controlled studies that address this important phase
of emergency treatment of heatstroke, namely cooling and hemodynamic management Therefore, the findings and rec-ommendations suggested above should be taken cautiously because they were derived mostly from observational case-series studies without control groups and involved a heteroge-neous population, with the probable presence of other con-founding factors
Trang 9Future directions
This study showed that most of the cooling techniques used
in the treatment of heatstroke were outdated and rudimentary,
whereas a new generation of cooling devices is now available
following the findings that induced hypothermia may be
bene-ficial in patients with neurologic injury, particularly post-cardiac
arrest [51] These innovative cooling techniques and devices,
which comprise infusion of large volumes of ice-cold
crystal-loid fluid (4°C), cooling catheters using ice-cold fluids
circulat-ing in a closed circuit, coolcirculat-ing helmets designed to cool the
brain, and cold-air or water pads and blankets controlled with
sophisticated algorithms, should prove to be of some benefit
to patients with heatstroke [51] However, their efficacy must
be rigorously tested in hyperthermic patients and not simply
extrapolated from studies on induced hypothermia Humans
regulate heat exchange with the environment by modulating
the blood flow through the cutaneous circulation Indeed,
hyperthermia is a high blood flow state due to
hypothalamus-mediated cutaneous vasodilatation, which is very different
from the familiar low blood flow profile observed in
post-car-diac arrest [43,51]
In the past decade, there has been substantial advance in the
understanding of the mechanisms of heatstroke injury at the
molecular and cellular levels [1] In addition to direct
cytotox-icity, it is suggested that heat triggers a complex
pathophysi-ology that involves alteration of heat shock responses,
exaggeration of the acute-phase response, and excessive
acti-vation of coagulation [1] Normalizing the body temperature
with cooling may not be enough to abrogate the inflammation,
coagulation activation, and progression to multiple organ
dys-function and death in more than a third of patients
[1,15,52,53] Therefore, in addition to improving the cooling
techniques, it is necessary to develop therapy based on
mod-ulation of the inflammatory and coagmod-ulation responses
[54-57] Immunomodulators such as interleukin-1 receptor
antag-onists, corticosteroids, and recombinant activated protein C
improve survival in the animal model of heatstroke but have yet
to be studied in humans [54-57]
Conclusion
This review revealed the need for more conclusive research
aimed at identifying the optimal cooling methods and
hemody-namic management of heatstroke Although the
recommenda-tions suggested should be taken cautiously, they were based
on a thorough review of the available evidence and hence
reflect the current state of knowledge Until further evidence is
established, these could serve as a practical approach for the
cooling and hemodynamic management of heatstroke, a
con-dition predicted to become more frequent in epidemic form in
the near future
Competing interests
The authors declare that they have no competing interests
Authors' contributions
AB made substantial contributions in the conception, design, acquisition, analysis, and interpretation of data MD pated in the acquisition and analysis of data EC-C partici-pated in the conception and design of data All authors drafted and revised the manuscript and have given final approval of the version to be published
Acknowledgements
This work was supported in part by the World Health Organization (WHO), Regional Office for Europe, and the EuroHEAT project cofi-nanced by DG Sanco (Directorate General for Health and Consumer Affairs) WHO, Regional Office for Europe was not involved in any part
of the study described in this manuscript.
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